title: Alpha-tocopherol succinate- and AMD3100-mobilized progenitors mitigate radiation combined injury in mice.
abstract: The purpose of this study was to elucidate the role of alpha-tocopherol succinate (TS)- and AMD3100-mobilized progenitors in mitigating combined injury associated with acute radiation exposure in combination with secondary physical wounding. CD2F1 mice were exposed to high doses of cobalt-60 gamma-radiation and then transfused intravenously with 5 million peripheral blood mononuclear cells (PBMCs) from TS- and AMD3100-injected mice after irradiation. Within 1 h after irradiation, mice were exposed to secondary wounding. Mice were observed for 30 d after irradiation and cytokine analysis was conducted by multiplex Luminex assay at various time-points after irradiation and wounding. Our results initially demonstrated that transfusion of TS-mobilized progenitors from normal mice enhanced survival of acutely irradiated mice exposed 24 h prior to transfusion to supralethal doses (11.5-12.5 Gy) of (60)Co gamma-radiation. Subsequently, comparable transfusions of TS-mobilized progenitors were shown to significantly mitigate severe combined injuries in acutely irradiated mice. TS administered 24 h before irradiation was able to protect mice against combined injury as well. Cytokine results demonstrated that wounding modulates irradiation-induced cytokines. This study further supports the conclusion that the infusion of TS-mobilized progenitor-containing PBMCs acts as a bridging therapy in radiation-combined-injury mice. We suggest that this novel bridging therapeutic approach involving the infusion of TS-mobilized hematopoietic progenitors following acute radiation exposure or combined injury might be applicable to humans.
authors.affiliation: Armed Forces Radiobiology Research Institute, Uniformed Services University of the Health Sciences, 8901 Wisconsin Ave, Bethesda, MD 20889-5603, USA.
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Singh
authors.forename: Stephen Y
authors.initials: SY
authors.lastname: Wise
authors.forename: Oluseyi O
authors.initials: OO
authors.lastname: Fatanmi
authors.forename: Lindsay A
authors.initials: LA
authors.lastname: Beattie
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Ducey
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Seed
mesh_terms: D000818:Animals; D001596:Benzylamines; D003131:Combined Modality Therapy; D000080027:Cyclams; D004307:Dose-Response Relationship, Radiation; D006571:Heterocyclic Compounds / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D009104:Multiple Trauma / Q000473:pathology / Q000517:prevention & control*; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods*; D011829:Radiation Dosage; D011832:Radiation Injuries / Q000473:pathology / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000008:administration & dosage; D015996:Survival Rate; D016896:Treatment Outcome; D014950:Wounds, Penetrating / Q000473:pathology / Q000517:prevention & control*; D024502:alpha-Tocopherol / Q000008:administration & dosage*
chemical_list: D001596:Benzylamines; D000080027:Cyclams; D006571:Heterocyclic Compounds; D011837:Radiation-Protective Agents; D024502:alpha-Tocopherol; C088327:plerixafor
keywords: cytokines; gamma-radiation; hematopoietic progenitor cells; mice; transfusion